Our results not only helped elucidate the molecular mechanism of JapA as a new class of NFAT1 inhibitor, but also would facilitate the validation of the therapeutic potential of targeting NFAT1 and NFAT1-MDM2 pathway, providing a basis for further preclinical and clinical development of NFAT1-MDM2 inhibitors for human cancer therapy. Here, NFATC2 is linked to cancer.